Dydrogesterone increases allopregnanolone in selected brain areas and in serum of female rats.

Objective To investigate the effects of dydrogesterone (DYD), a synthetic progestin largely used in hormone therapy, on the central nervous system by studying two markers of the neuroendocrine function: the neurosteroid allopregnanolone and the opioid β-endorphin. Design Experimental study on animal model. Setting Academic research environment. Animal(s) 72 Wistar female rats. Intervention(s) One group of fertile and one of ovariectomized rats (receiving placebo) were used as control. After ovariectomy, the rats underwent a 2-week oral treatment of DYD (0.2, 0.6, or 1.0 mg/kg per day), alone or with estradiol valerate (E2V; 0.05 mg/kg per day). Main Outcome Measure(s) Allopregnanolone and β-endorphin, assessed in different brain areas and in circulation. Result(s) Ovariectomy decreased allopregnanolone anywhere except in the adrenal gland and reduced β-endorphin central levels; E2V reversed the effects of ovariectomy; and DYD (1 mg/kg per day) increased allopregnanolone levels in frontal lobe, hippocampus, and hypothalamus. Combined administration of DYD at 1 mg/kg per day plus E2V determined a further increase of allopregnanolone levels in frontal lobe, hippocampus, hypothalamus, and serum. Dydrogesterone did not modify the levels of β-endorphin induced by E2V. Conclusion(s) Dydrogesterone interacts with allopregnanolone levels (less with β-endorphin), and it can be considered important modulator of the neuroendocrine function.